The broad aim of this project is to investigate in detail the effects of maternal diabetes mellitus on carbohydrate and lipid metabolism in livers of the term fetuses and newborn rats. This investigation will center around three major areas: (1) the development of hepatic glycogen metabolism, (2) the development of hepatic lipogenesis, and (3) the development and regulation of hepatic gluconeogenesis in the term fetuses and newborn rats. Furthermore, kinetics of a premature induction in utero by glucagon and c-AMP and a normal development immediately after birth of hepatic PEP-carboxykinase will be studied using the specific antibody against this enzyme. Experimental diabetes mellitus in female rats will be induced by injecting streptozotocin prior to or immediately after initiation of pregnancy. In addition to the "normal" control group, the diabetic pregnant rats receiving daily maintenance dose of insulin will be also included as the "treated" control group. The effects of maternal diabetes on the fetal development such as the total DNA, fat, protein and water content will be studied. The development patterns of glycogen content and of several key enzymes such as glycogen synthetase (active + inactive), phosphorylase (active + inactive) involved in glycogen metabolism in livers of fetuses and newborns of diabetic rats will be investigated. BY injecting 14C-glucose directly into the fetuses, glycogen synthesis in vivo will also be studied. Hepatic lipid synthesis both in vivo and in vitro as well as the development pattern of several key lipogenic enzymes will be investigated. The turnover of hepatic PEP-carboxykinase during its normal development immediately after birth and also during its premature induction in utero by glucagon or c-AMP injection will be studied. This enzyme will be labeled by injecting 14C-leucine, and it will be precipitated by the specific antibody made against rat liver PEP-carboxykinase. For changes in hepatic metabolites, liver will be freeze-clamped in situ, and metabolites will be quantitated.